Extracorporeal photopheresis combined with pentostatin in the conditioning regimen for canine hematopoietic cell transplantation does not prevent GVHD

摘要

Extracorporeal photopheresis (ECP) and the purine analog pentostatin exert potent immunomodulatory effects. We evaluated the use of these treatment modalities to prevent GVHD in a canine model of unrelated dog leukocyte antigen mismatched hematopoietic cell transplantation (HCT), after conditioning with 920 cGy total body irradiation (TBI). We have shown previously in this model that 36/40 dogs given methotrexate (MTX) alone as postgrafting immunosuppression engrafted and that 25 of 40 dogs had severe GVHD and median survival of 21 days. In the current study, 9 dogs received conditioning with 920 cGy TBI and postgrafting MTX either with ECP on days −2 to −1 alone (n=5) or ECP on days −6 and −5 combined with 2 doses of pentostatin (days −4 to −3) (n=4). Seven of 9 dogs achieved engraftment. Six dogs developed severe acute GVHD (4 in the group with ECP alone and 2 with Pentostatin and ECP). We failed to demonstrate a positive impact of ECP and pentostatin for the prevention of GVHD compared to historical control dogs.